Sanguinarine enhances cisplatin sensitivity via glutathione depletion in cisplatin‐resistant ovarian cancer (A2780) cells

Sarkhosh Inanlou, R and Shafiei Irannejad, V and Mohammadzadeh, A and Molaparast, M (2019) Sanguinarine enhances cisplatin sensitivity via glutathione depletion in cisplatin‐resistant ovarian cancer (A2780) cells. Chem Biol Drug Des, 00. pp. 1-9.

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Abstract

Ovarian cancer is considered as one of the most lethal gynecological cancers, and cis- platin‐based therapy has an important role as the first‐line option for chemotherapy. Resistance to chemotherapy is the main obstacle against successful cancer chemo- therapy with cisplatin. Therefore, identifying potent compositions and molecules with fewer side‐effects is a big challenge to overcome cisplatin resistance. In this study, we investigated the possible mechanism and potency of sanguinarine, a plant‐ derived alkaloid, in human cisplatin‐resistant ovarian cancer (A2780/R) cells. The effect of sanguinarine on cytotoxicity of cisplatin was determined by MTT assay. Apoptosis‐inducing effect of sanguinarine alone and in combination with cisplatin was evaluated by annexin V/PI assay and DAPI staining. Intracellular glutathione (GSH) content was quantitated using GSH assay kit after treatment with sanguinar- ine. Results indicated that sanguinarine enhances the sensitivity of A2780/R cells to cisplatin. Apoptosis‐inducing effect of cisplatin was also enhanced when combined with sanguinarine. Furthermore, sanguinarine reduced intracellular GSH content in a dose‐dependent but not time‐dependent manner. These findings suggest that sangui- narine could reverse cisplatin resistance in A2780/R cells through GSH reduction. Therefore, sanguinarine can be used as one of the potent adjuvants for ovarian cancer chemotherapy.

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